Figure 4.

The existence of stresses that alleviate average mutation effects could imply that
there is average epistasis between mutations. Average absolute growth rates of the
parental strain (with no mutations) and of the mutant library (defined as having an
average of 1 unit of mutation per mutant in the library) are shown under favorable
conditions (black) and under trimethoprim stress (gray). Linear extrapolation (dashed)
of the data, assuming an absence of epistasis, would lead to intersection of the lines.
Such an intersection seems unrealistic, however, as it would imply an increase of
the average absolute growth rate under stress. To avoid intersection at least one
of the lines must bend, which would reflect the existence of average epistatic interactions
between mutations. Note that the fact that our library may contain a variable number
of mutations per genome does not affect the argument presented above.